Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.     

Retroviral gene transfer is inhibited by chondroitin sulfate proteoglycans/glycosaminoglycans in malignant pleural effusions

Gene therapy may be an important adjuvant for treating cancer in the pleural space. The initial results of retroviral gene transfer to cancer cells in malignant pleural effusions revealed that transduction was markedly inhibited, and studies to characterize the inhibitory factor(s) were performed. The inhibition was contained within the soluble, rather than cellular, components of the effusions and was demonstrated with amphotropic, gibbon ape leukemia virus, and vesicular stomatitis virus-glycoprotein pseudotyped retroviral vectors. After excluding complement proteins, a series of studies identified chondroitin sulfates (CSs) as the inhibitory substances. First, treatment of the effusions with mammalian hyaluronidase or chondroitinases, but not Streptomyces hyaluronidase, abolished the inhibitory activity. Second, addition of exogenous CS glycosaminoglycans mimicked the inhibition observed with pleural effusions. Third, immunoassays and biochemical analyses of malignant pleural effusion specimens revealed CS in relevant concentrations within pleural fluid. Fourth, proteoglycans/glycosaminoglycans isolated from the effusions inhibited retroviral gene transfer. Analyses of the mechanism of inhibition indicate that the chondroitin sulfates interact with vector in solution rather than at the target cell surface. These results suggest that drainage of the malignant pleural effusion, and perhaps enzymatic pretreatment of the pleural cavity, will be necessary for efficient retroviral vector mediated gene delivery to pleural metastases.     

Acute mast cell leukemia disclosed by vasomotor flushing

INTRODUCTION: Acute mast cell leukemia is a rare and severe disease. We report herein a case associated with a flush syndrome. CASE REPORT: A 44-year-old man, presented with a flush of face and trunk. Bone marrow was infiltrated with immature mast cells. In spite of chemotherapy and bone marrow transplantation the patient deceased. DISCUSSION: Pheochromocytoma, carcinoid tumor, and mastocytosis are associated with a flush syndrome. In our patient the diagnosis was an acute mast cell leukemia. Acute mast cell leukemia can follow systemic mastocytosis or occur de novo. This disease is of poor prognosis. No treatment is available.     

Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma

Late occurrence of cytomegalovirus (CMV) disease after day 100 after bone marrow transplantation has become an increasing problem; whether a quantitative measurement of CMV DNA in plasma by polymerase chain reaction (P-PCR) could be predictive of such disease was investigated. In a prospective study, 117 subjects undergoing allogeneic marrow transplantation were followed for 120 days with weekly CMV blood cultures, with day 35 bronchoalveolar lavage CMV cultures, with weekly CMV P-PCR, and with clinical follow-up for an additional 1-2 years. Despite preemptive ganciclovir, CMV disease occurred in 9% of subjects, with a median time of onset of 176 days. Quantitative CMV P-PCR was associated with the late development of CMV disease (P = .01). Of 43 subjects with positive P-PCR results, 23% developed CMV disease, but no disease occurred in the 74 subjects with negative P-PCR (P < .001), despite the fact that 22% had CMV isolated from lung lavage fluid and 32% had CMV isolated from blood.     

Diagnosis of hemochromatosis probands in a community hospital

PURPOSE: To evaluate factors that lead to the diagnosis of hemochromatosis probands in a community hospital, including education of physicians about hemochromatosis and iron overload, specialty of physicians, diagnostic indicators of hemochromatosis, and clinical manifestations of hemochromatosis probands. PATIENTS AND METHODS: We conducted a hemochromatosis education program for health care personnel associated with a community hospital and the public during 1990 to 1994. Data on physicians who diagnosed probands, diagnostic indicators of hemochromatosis, and manifestations of hemochromatosis and associated illnesses were tabulated. Iron grades of all hospital liver biopsy specimens obtained from Caucasian subjects during 1990 to 1994 were also analyzed. RESULTS: We identified 162 hemochromatosis probands; 66.7% were diagnosed by physicians who participated in our education program. Primary care and internal medicine subspecialty physicians diagnosed 66.7% and 29.6% of probands, respectively, based on elevated serum iron parameters and hepatic enzyme concentrations (51.9% and 36.4% of probands, respectively). Iron overload occurred in 90.7%, and was associated with clinical manifestations in most. Of 844 hospital liver biopsy specimens from Caucasians, 8.5% had increased iron grades; 4.6% represented hemochromatosis. CONCLUSIONS: Physicians with current education readily diagnose hemochromatosis probands during routine health care delivery, but most probands identified in this manner have iron overload. Our results suggest that community physicians and hospitals could contribute substantially to hemochromatosis screening programs, permitting detection of more homozygotes before the development of iron overload.     

Identification of urinary dipeptidase as the released form of renal dipeptidase

Beckwith-Wiedemann syndrome (BWS) comprises of a number of childhood abnormalities, often associated with one or more tumors. Thirty-eight patients were investigated to determine clinical and/or biological signs associated with a tumor presence. Our patients exhibited a higher incidence of tumor development (21%) than that previously reported, underlying the care with which such patients should be followed, when particular clinical features are observed: visceromegaly affecting three organs (liver, kidney, spleen), and also family history with sign of BWS such as macroglossia, omphalocele, hemihypertrophy, embryonic tumor), high body weight at birth (> or = +2 standard deviations and diastasis recti.     

AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.